Journal: American Journal of Cancer Research
Article Title: Ubiquitin-specific peptidase 2a (USP2a) deubiquitinates and stabilizes β-catenin
doi:
Figure Lengend Snippet: USP2a upregulates β-catenin protein and promotes its transcriptional activity. A. Each SFB-tagged deubiquitinase was co-transfected with MYC-tagged β-catenin into HEK293T cells, followed by pulldown with S-protein beads and immunoblotting with antibodies against FLAG and MYC. B. Either β-catenin-responsive TOPflash or its mutant FOPflash construct was co-transfected with each SFB-tagged deubiquitinase and Renilla luciferase into HEK293T cells. A dual luciferase assay was used to determine β-catenin activity. Firefly luciferase activity was normalized to Renilla luciferase activity. MYC-tagged β-catenin serves as a positive control. Error bars are S.D. C. SFB-tagged GFP, USP2a, USP26, and USP42 were co-transfected with MYC-tagged β-catenin into HEK293T cells, and pulled down with S-protein beads. Antibodies against MYC and FLAG were used to detect β-catenin and DUBs. CypB (cyclophilin B) serves as the loading control. D. Left panel: luciferase reporter assay validating that the 4 candidate deubiquitinases (USP2a, USP36, DUB3, and OTUD7B) promote the transcriptional activity of β-catenin. Error bars are S.D. ***: P < 0.001. Right panel: immunoblotting of HSP90 and SFB-tagged GFP, USP2a, USP36, DUB3, and OTUD7B in HEK293T cells. HSP90 serves as the loading control. T: TOPflash; F: FOPflash. E. Each SFB-tagged candidate deubiquitinase was co-transfected with HA-tagged ubiquitin and MYC-tagged β-catenin into HEK293T cells. After MG132 treatment for 6 hours, β-catenin was immunoprecipitated with a MYC-specific antibody, followed by immunoblotting with antibodies against HA and MYC. F. Immunoblotting of β-catenin, FLAG, and HSP90 in HEK293T cells transfected with SFB-tagged GFP, USP2a, USP36, DUB3, or OTUD7B. G. qPCR of CTNNB1 (the gene that encodes β-catenin) in HEK293T cells transfected with the empty vector, wild-type USP2a, or the catalytically inactive mutant (C276A). Error bars are S.D. n.s.: not significant. H. Immunoblotting of USP2a, β-catenin, and CypB in BT549 cells transduced with USP2 shRNAs. I. Immunoblotting of USP2a, β-catenin, and CypB in BT549 cells transduced with USP2 shRNA with or without ectopic expression of USP2a.
Article Snippet: HA-ubiquitin, TOPflash, and FOPflash constructs were from Addgene (plasmid number: 17608, 12456, and 12457).
Techniques: Activity Assay, Transfection, Western Blot, Mutagenesis, Construct, Luciferase, Positive Control, Control, Reporter Assay, Ubiquitin Proteomics, Immunoprecipitation, Plasmid Preparation, Transduction, shRNA, Expressing